Symptoms and General Pathology

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Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Gland and Hormone Related Diseases

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Infertility

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Testicular Neoplasms

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Genital Diseases, Male

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Female Urogenital Diseases and Pregnancy Complications

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Methyltestosterone

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Testosterone

Testosterone undecanoate

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Castor Oil

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Castor

Testosterone undecanoate 1000mg injection at baseline (0-week), 6-week, 18-week, 30-week

Injection 4 ml of castor oil at baseline (week-0), week-6, week-18, week-30

Testosterone undecanoate 1000mg (in 4 ml of castor oil injections) at baseline (0-week), 6-week, 18-week, 30-week

4 ml of Castor Oil injected at baseline (0-week), 6-week, 18-week, 30-week.

Andrea Lenzi, MD

Andrea Isidori, MD, PhD

Vincenzo Bonifacio, MD, PhD

Patients with infertility often presents alterations at ultrasonographic examination of the testis. These alterations include a much higher incidence of small, multiple, non-palpable hypoechoic micro-nodules that can show internal vascularization. This finding often create alarm and anxiety, because it has to be placed in a differential diagnosis versus low-stage malignant germ cell tumors. Nevertheless, explorative surgery reveal that a consistent number of these lesion are benign, due to Leydig cell hyperplasia or Leydig cell tumours. The purpose of this study is to evaluate the effects of androgen therapy on the size and number of non-palpable hypoechoic micro-nodules in patients with elevated gonadotropin levels.

Patients with the testicular dysgenesis syndrome, that comprises a variable spectrum of clinical manifestations, such as infertility, cryptorchidism, hypospadias, impaired spermatogenesis and testicular germ cell neoplasms, often develop alterations in the Leydig cell compartment. These alterations range from abnormal localization and clustering to hyperplasia or tumorous formation.

Leydig cell tumors (LCTs), although uncommon in the general population, are the most frequent non-germ cell testicular neoplasms, and their incidence has been reported increasingly growing, especially in infertile patients. Given that the focal areas of Leydig cell hyperplasia are nowadays easily detectable at ultrasonography of the testis (US), as small non-palpable hypoechoic micro-nodules that can show internal vascularization, their finding create a diagnostic challenge versus low-stage malignant germ cell tumors.

Patients with testicular dysgenesis syndrome in general exhibit an elevation of Follicle-Stimulating Hormone (FSH), but in these patients, very frequently, even Luteinizing Hormone (LH) is above the reference range. The latter can work as a growth factor for Leydig cells. Since exogenous testosterone can suppress LH levels, it could be that androgen therapy could revert the LH-induced growth stimulation of Leydig cell compartment.

The purpose of this study is to evaluate the effects of androgen therapy on the size and number of non-palpable hypoechoic micro-nodules in patients with elevated gonadotropin levels.

The purpose of this study is also to evaluate whether the behavior (UltraSonographic appearance, US) of the non-palpable hypoechoic micro-nodules during a 4-month trial of testosterone therapy can offer a novel diagnostic tool in the differential diagnosis of benign versus malignant testicular nodules.

The trial will be open only for patients with multiple non-palpable hypoechoic micro-nodules that have an elevation of both FSH and LH and that are not seeking conception.

Participants in the study will be randomized to one of two treatment groups, receiving either testosterone undecanoate (low-dose androgen) or placebo, for two 6 months. All participants will be evaluated for safety at the beginning of the study and at 2, 4, and 6 months with careful history, physical examination, blood sampling and testicular ultrasonography. Patients will also be offered the possibility to perform Magnetic Resonance Imaging (MRI) of the testis at baseline and after treatment, and/or surgical enucleation of the lesions.

Androgen for Leydig Cell Proliferation

Androgen Treatment in Leydig Cell Proliferation

Percentage change of the area of the lesions multiplied by the number of the measured lesions: \[(area_1 + area_2 + area_3 + ... + area_n)\*n\].

The latter measure account for reduction in the number of lesions (disappearance).

Percentage change in the area of the lesion (measured with computer assisted graphics).

Reduction of the serum Luteinizing Hormone (LH) levels during testosterone therapy

Evaluation of sperm cell production after testosterone withdrawal.

Changes in the number of areas / nodules / lesions in the long-term safety assessment

University of Roma La Sapienza

Professor of Endocrinology

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Androgen for Leydig Cell Proliferation	NCT01206270	Klinefelter Syn... Hypergonadotrop... Hypergonadotrop... Hypergonadotrop...	Testosterone un... Castor Oil	18 Years - 60 Years	University of Roma La Sapienza
Androgen for Leydig Cell Proliferation	NCT01206270	Klinefelter Syn... Hypergonadotrop... Hypergonadotrop... Hypergonadotrop...	Testosterone un... Castor Oil	18 Years - 60 Years	University of Roma La Sapienza

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